DESCRIPTION: The applicant will thoroughly characterize the murine mucosal and systemic responses (cellular and humoral) generated by immunization with HIV envelope protein, and the effectiveness of IL-12 as an adjuvant for the production of immunity at mucosal surfaces will also be examined. In Aim 1, the ability to enhance mucosal immunity by co-administering recombinant IL-12 with HIV gp160 via the oral and intranasal route will be assessed. In Aim 2, DNA IL-12 will be delivered either mucosally or remotely by IM or gene gun, and similar characterizations of immune responses will be performed. In Aim 3, experiments will examine the potential dysregulation of mucosal immune responses by immunization with rgp160 in combination with IL-12 protein or the plasmid DNA-IL-12.